反应详情

To a suspension of 6-[(2,2-diphenylethyl)amino]-9-(tetrahydro-2H-pyran-2-yl)-9H-purine-2-carbonitrile (176 g, 0.415 moles) (Preparation 13) in industrial methylated spirits (770 ml) was added a solution of sodium hydroxide (33.3 g, 0.83 moles) in deionised water (110 ml). The resultant slurry was heated under reflux for 2.5 hours during which time a clear solution formed. The mixture was allowed to cool to ambient temperature over 16 hours which resulted in the formation of a precipitate. Water (200 ml) was then added, and the mixture was distilled at atmospheric pressure. Over the course of the distillation, water (500 ml) was added periodically to the mixture, and a total of 720 ml of distillate was collected. The resultant mixture was allowed to cool slowly to ambient temperature with stirring and a thick precipitate formed. The slurry was cooled in an ice-bath, and the solid was collected by filtration. The filter cake was washed with a solution of deionised water (225 ml) and industrial methylated spirits (25 ml). The damp filter cake was suspended in a mixture of deionised water (965 ml) and dichloromethane (965 ml) and the pH of the mixture was adjusted to pH 1.2 by the addition of concentrated hydrochloric acid. The phases were separated and the aqueous layer was extracted with dichloromethane (300 ml). The organic phases were combined and the solvent was distilled at atmospheric pressure until 750 ml of distillate had collected. Ethyl acetate (1100 ml) was added and distillation was continued until a further 750 ml of distillate had collected and an off-white precipitate had formed. The resulting slurry was allowed to cool to ambient temperature and was further cooled in an ice-bath. The solid was collected by filtration and the filter cake was washed with chilled ethyl acetate (2×350 ml). The resultant solid was dried in an oven at 70° C. under reduced pressure to give the title compound as an off-white solid (163 g), m.p. 155° C. (with decomposition).

1. temperatureThe resultant slurry was heated
2. temperatureunder reflux for 2.5 hours during which time a clear solution
3. customformed
4. customresulted in the formation of a precipitate
5. distillationthe mixture was distilled at atmospheric pressure
6. distillationOver the course of the distillation, water (500 ml)
7. additionwas added periodically to the mixture
8. distillationa total of 720 ml of distillate was collected
9. temperatureto cool slowly to ambient temperature
10. customa thick precipitate formed
11. temperatureThe slurry was cooled in an ice-bath
12. filtrationthe solid was collected by filtration
13. washThe filter cake was washed with a solution of deionised water (225 ml) and industrial methylated spirits (25 ml)
14. additionThe damp filter cake was suspended in a mixture of deionised water (965 ml) and dichloromethane (965 ml)
15. additionthe pH of the mixture was adjusted to pH 1.2 by the addition of concentrated hydrochloric acid
16. customThe phases were separated
17. extractionthe aqueous layer was extracted with dichloromethane (300 ml)
18. distillationthe solvent was distilled at atmospheric pressure until 750 ml of distillate
19. customhad collected
20. additionEthyl acetate (1100 ml) was added
21. distillationdistillation
22. customhad collected
23. customan off-white precipitate had formed
24. temperatureto cool to ambient temperature
25. temperaturewas further cooled in an ice-bath
26. filtrationThe solid was collected by filtration
27. washthe filter cake was washed with chilled ethyl acetate (2×350 ml)
28. customThe resultant solid was dried in an oven at 70° C. under reduced pressure